Previous observations of the variation associated with the acute insulin response suggested that this phenotype was controlled by one or more genes. Glucokinase, which has been linked to the MODY (maturity onset diabetes of the young) form of diabetes, has been proposed as an intracellular glucose sensor, a likely candidate gene contributing to variations in glucose stimulated insulin responses. Similarly, GLUT2, the major glucose transporter of the pancreas could also be responsible for the variation observed in the acute insulin response. Polymorphisms at both of these genes have been examined for an association or linkage with the acute insulin response. Certain alleles of GLUT2 have been associated with the acute insulin response, and analysis of over 90 sibpairs suggests there is linkage between this region on chromosome 3 and the acute insulin response. Currently, a structural analysis of the coding regions for the gene encoding GLUT2 is underway.